The first component of human complement (C1) readily dissociates under physiologic conditions into two subunits - C1q and C1r2C1s2. The equilibrium constant for this reaction has been determined for native C1 in fresh normal human serum by hemolytic titration. Standard technology was modified to simulate physiologic conditions. Furthermore, assays were carried out at numerous poncentrations of sensitized erythrocytes, thereby allowing the calculation of the percent of associated C1 at different total C1 concentration. Increased C1 dissociation was observed with dilution. From these data, an association constant of 4.5 × 108 M−1 was calculated for native C1. Thus in normal human serum approximately ten percent of the C1 is present as free C1q and C1r2C1s2.